A fundamental new view of local tissue heat transfer has been developed which theoretically and experimentally indicates that the principal vascular elements involved in blood-tissue energy exchange in muscle tissue are the 100 to 500 mum arteries an their countercurrent veins. A new bioheat equation has been derived to describe this energy exchange and a new model for peripheral tissue heat transfer proposed in which it is possible for the first time to quantitatively relate the heat transfer between blood and tissue to the local microvascular hemometry and flow. In the proposed research we will develop a theoretical and conceptual framework in which the microvascular description an be used to relate changes in local tissue conductivity to the centrally and locally mediated changes in the vasomotor tone of the microcirculation. In the proposed research the local thermal modulation of - and beta-adrenoceptor mediated control of microvascular blood flow will be experimentally examined in muscle and the results interpreted using this new equation an peripheral tissue model. In particular, (i) a new experimental microvascular model will be developed in which the heat transfer from vascular elements 40-120 mum in diameter can be individually examined with high resolution infra-red thermography to experimentally determine the role of blood flow and vessel size on local tissue conductivity, keff, and thus test the predictions of the Weinbaum-Jiji equation for keff; (ii) pharmacological techniques will be used to examine the role of mu1, mu2, and beta2 adrenoceptor mediated responses under normo-, hyper- and hypothermic conditions in the microvascular preparations and the results will be applied to the theory developed in (i) to model these responses. The proposed studies will have a significant impact upon both basic and applied problems in thermal physiology. The experimental qualification of heat transfer in 40-120 mum vessels will yield the first data for vessels of this size class, and will permit evaluation of the large amount of theoretically work that has been carried out over the past 40 years. The proposed studies will have a major impact upon the conceptualization of the mechanism of the vascular contributions to the thermoregulatory effector response and will impact upon the improvement of the clinical use of hyperthermia in the treatment of cancer.